Generation, genomic characterization, and differentiation of triploid human embryonic stem cells.
Stem Cell Reports
; 18(5): 1049-1060, 2023 05 09.
Article
en En
| MEDLINE
| ID: mdl-37116485
ABSTRACT
Humans are diploid organisms, and triploidy in human embryos is responsible for â¼10% of spontaneous miscarriages. Surprisingly, some pregnancies proceed to triploid newborns that suffer from many neuro-developmental disorders. To investigate the impact of triploidy on human development, we generate triploid human embryonic stem cells (hESCs) by fusing isogenic haploid and diploid hESCs. Comparison of the transcriptome, methylome, and genome-wide replication timing shows general similarity between diploid and triploid hESCs. However, triploid cells have a larger volume than diploid cells, demonstrating decreased surface-area-to-volume ratio. This leads to a significant downregulation of cell surface ion channel genes, which are more essential in neural progenitors than in undifferentiated cells, leading to inhibition of differentiation, and it affects the neuronal differentiation ability of triploid hESCs, both in vitro and in vivo. Notably, our research establishes a platform to study triploidy in humans and points to their pathology as observed in triploid embryos.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Triploidía
/
Células Madre Embrionarias Humanas
Límite:
Female
/
Humans
/
Newborn
/
Pregnancy
Idioma:
En
Revista:
Stem Cell Reports
Año:
2023
Tipo del documento:
Article
País de afiliación:
Israel